|PROSITE documentation PDOC51735 [for PROSITE entry PS51735]|
The Filoviridae family of viruses [E1], which includes marburgvirus (MARV) and ebolavirus (EBOV), can cause intermittent outbreaks that often result in high fatality rates. The family consists of five species of EBOV, Zaire, Reston, Sudan, Taļ Forest, and Bundibugyo; one species of MARV; and a proposed genus Cuevavirus possessing a single species Lloviu cuevavirus. MARV and EBOV share a common genome organization but show important differences in replication complex formation, cell entry, host tropism, transcriptional regulation, and immune evasion [1,2,3,4].
Filoviruses counteract innate immunity through the multifunctional viral protein (VP) 35 proteins, which perform critical roles in viral RNA synthesis, virus assembly, and virus structure. VP35 contains an N-terminal coiled-coil domain required for its oligomerization and a C-terminal interferon (IFN) inhibitory domain (IID). Mutations within the VP35 IID result in loss of host immune suppression. The N-terminus provides a critical oligomerization function, which facilitates efficient IFN inhibition through elements located at the C-terminus of VP35. The VP35 IID can also bind dsRNA and VP35-mediated IFN antagonism correlates with dsRNA-binding activity [1,2,3,4].
The VP35 IID is made of a stretch of about 120 residues that folds independently. The VP35 IID structure is organized into 2 subdomains: an N-terminal α-helical subdomain and a C-terminal β-sheet subdomain (see <PDB:3FKE>). The α helical subdomain consists of a four helix bundle, while the β sheet subdomain is formed by four antiparallel β strands as well as an α helix and a type II polyproline helix. The VP35 IID structure contains 2 basic patches that are highly conserved among members of the Filoviridae family. The first basic patch is located in the helical subdomain and its functional significance remains unknown. The second one, the so-called central basic patch, is located in the β sheet subdomain and contains residues that are required for dsRNA binding and IFN inhibition [2,3,4].
The profile we developed covers the entire VP35 IID.Last update:
October 2014 / New entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Leung D.W. Ginder N.D. Nix J.C. Basler C.F. Honzatko R.B. Amarasinghe G.K.|
|Title||Expression, purification, crystallization and preliminary X-ray studies of the Ebola VP35 interferon inhibitory domain.|
|Source||Acta Crystallogr. F 65:163-165(2009).|
|2||Authors||Leung D.W. Ginder N.D. Fulton D.B. Nix J. Basler C.F. Honzatko R.B. Amarasinghe G.K.|
|Title||Structure of the Ebola VP35 interferon inhibitory domain.|
|Source||Proc. Natl. Acad. Sci. U.S.A. 106:411-416(2009).|
|3||Authors||Leung D.W. Prins K.C. Basler C.F. Amarasinghe G.K.|
|Title||Ebolavirus VP35 is a multifunctional virulence factor.|
|4||Authors||Ramanan P. Edwards M.R. Shabman R.S. Leung D.W. Endlich-Frazier A.C. Borek D.M. Otwinowski Z. Liu G. Huh J. Basler C.F. Amarasinghe G.K.|
|Title||Structural basis for Marburg virus VP35-mediated immune evasion mechanisms.|
|Source||Proc. Natl. Acad. Sci. U.S.A. 109:20661-20666(2012).|